Detective Mac Taylor is shown jogging down a street because he cannot sleep. The scene then changes to a janitor pushing a cart down a hallway. The janitor then enters a room with many storefront mannequins. He then turns on a cassette tape player and begins dancing a tango with one of them. When he does a dip move her head falls off and rolls away. When he kneels down to find the head he finds the body of a woman with green hair lying dead with a gunshot wound to the head.
The scene changes to one of the crime scene investigators snapping photos of the dead woman. During their initial inspection of the body Mac receives another unknown call at 3:33 on his mobile phone.
The team finds a small piece of bamboo, a tick under her skin, and a small male doll with the word "Johnny" on the shirt. The bullet appears to have been fired from a suppressed .45 Caliber pistol, most likely a suppressed Colt M1911. It is believed she was tortured to death because her arms were bound and there were scalpel cuts on her neck. After doing an image search on Google for this unknown woman it is revealed that she is part of a virtual world known as Second Life. Her avatar is named Venus and she is very famous on Second Life. Mac asks Danny to contact Second Life to acquire her real life information.
She is revealed to be Cheryl Miller, a resident of New York who did most of her living on Second Life. She had a Second Life partner named Don Juan 2-3 whom she was planning to meet for the first time at a nightclub called Random. Don Juan 2-3 is revealed to be Jonathan O'Dell, however his credit card he used on Second Life is expired and he has an unknown address.
Mac then decides the best thing to do to find Johnny O'Dell is to enter Second Life himself. Adam helps Mac create his Second Life avatar. Mac continuously gives Adam odd looks implying he thought this was silly. Adam then takes the keyboard away from Mac to speed up the registration process. Mac is suddenly thrown into a Welcome Area and attempts to contact the infamous "White Rabbit".
Meanwhile, Stella and Lindsay discover the tick has lyme disease. They believe the killer may have lyme disease and may be a hunter. Mac and Adam finally speak to The White Rabbit, but he will only tell them where Johnny is if they pay him 6,000 linden dollars. After they pay him he teleports them to Shangri-La where they finally locate Don Juan 2-3. When Mac greets him he says "Goodbye" and flies away. They determine that if they want his attention that they should approach him as a female. After a quick gender change they approach Don Juan 2-3 again. Mac proves to be very ineffective speaking as a woman, so Stella steps in and successfully holds him long enough so they can trace his IP address.
When they show up at the shop Johnny is hiding in his friend at the front tries to warn him via instant messenger that the cops came in. He attempts to flee from the police but ends up running into someone and tripping knocking a gun out of his backpack.
Stella and Danny begin questioning Johnny. When shown a picture of Cheryl Miller, Johnny claims he has never seen her before. When shown a picture of Venus (her Second Life avatar) Johnny immediately identifies her as such. Johnny tells them that he is in love with Venus, which they do not believe is possible. They ask Johnny if he is a hunter and he shakes his head. Mac first believes that he is exibiting symptoms of lyme disease. Johnny tells Stella that the plan was to meet Cheryl at the club "Random". They showed Johnny the doll they found and he admitted he made it so Cheryl would know what he really looks like when they met. Johnny then reveals he is dying from acute multiple sclerosis and says that is the reason he bailed out of meeting Cheryl. Johnny implied he had the gun in his possession for the purpose of suicide, since his condition is uncureable. A problem arises when they discover that Johnny is still talking to Venus on Second Life long after Cheryl was murdered.
Sheldon processes the bullet, but is unable to match it to Johnny's gun. Stella asks him to check the bullet to see if the gun has been used in other murders.
Mac and Adam return to Second Life to track down Venus. Mac is suddenly stopped by an avatar named Cezar. Cezar will not let Mac through unless he has a battle in his colosseum. Mac enters the arena with armor on to a cheering croud of spectators. Adam tells Mac he does not stand a chance of winning, so Mac agrees to turn over control of his avatar to Adam. Adam engages in battle with the other competitors and ends up defeating them all. Mac then searches for Venus and finds her next to a fountain. When they try to ping her IP address they are unable to because she is Wi-Fi fishing. Suddenly a griefer dressed as a wolf furry pops up and aims a gun at Venus and says "Stop pretending to be Venus!". The griefer takes several shots at Venus making her avatar disappear into the ground. When Mac attempts to question the griefer he runs away and hops onto a hoverboard. Adam gives Mac a jetpack and chases the wolf. The chase suddenly ends when the wolf is frozen in mid-air and does not reply to Mac's questions. Adam tells Mac that the wolf either lost his internet connection or his computer crashed. However Adam is able to trace the wolf's IP address to an apartment.
The police go to the apartment and get no response from inside. Mac decides to throw a four-way camera device inside. On the camera they see someone slumped over a laptop computer. When they lift him up they are shocked to see that Johnny O'Dell has been murdered with a bullet to the head.
Sheldon has positively matched the bullet that killed Cheryl to the one that killed Johnny. Stella theorizes that the killer didn't want any information from Johnny because he was not tortured as Cheryl was. Stella believes Johnny was killed because he was blowing the assassin's cover. Sheldon informs Stella that he did get a hit on their bullets from another murder of a high profile judge murdered last week. Judge McHenry never returned from a hunting trip and the police thought it was a hunting accident. This might explain the tick found on Cheryl's body.
Mac returns to Second Life again and looks at the shoes that Venus dropped when she disappeared. On the heels of the shoes he discovers a logo for "Old Gearhead", the Second Life vendor who created the shoes.
Following this lead Stella and Danny go to a mechanic shop in real life to talk to the maker of the shoes. The mechanic states that Venus is not a regular customer but he still treats her special. He informs the CSI that she has a date tonight on Second Life with Mr. TCB. Suddenly Venus walks into his virtual store and tells him that she wants to replace her shoes she lost.
Meanwhile Lindsay tells Mac that the bamboo they found is used in certain types of buildings. Mac says they need to start searching for new buildings that have not treated their bamboo yet. Stella calls Mac and informs him that they found Venus again on Second Life. Mac quickly runs to get back on Second Life. He asked Venus if they can speak somewhere in private. Venus agrees and he follows her through a red curtain. Mac proceeds to walk down a hallway but Venus appears to have disappeared. She taunts him "You won't find me, Detective Taylor." She claims The White Rabbit told her everything. Suddenly the pictures on the walls flip around, each showing one of the murder victims. One by one each picture has a silenced gunshot wound and a scream. Mac looks down on the floor and sees a "calling card". Adam tells Mac to pick it up then quickly changes his mind and says the calling card could be bad. Suddenly Venus comes out of the floor and begins mimicking Mac's avatar in both voice and appearance. The avatar starts duplicating itself over and over convincing him that he received a virus. Mac tells Adam to turn on a firewall, but it is too late and the CSI computer network becomes infected. Mac demands Adam log off Second Life but he refuses, because he didn't want Venus to get away. The computers fail and suddenly go black.
Adam informs everyone that the computers won't be back online for another hour and Lindsay is worried that Venus will change avatars by then. Stella says she doesn't think that will happen because the assassin needs Venus for some reason. Mac states that it's Venus's popularity that the assassin needs to get to her next target. They find out Mr. TCB's real life information and discover he is being used by U.S. Congressman DeVayne. His secretary informs CSI that he is in New York City and gives them his current address and mobile phone number. Mac attempts to call Congressman DeVayne but gets no reply. They find out the apartment is new and rush out to find him. They know that the assassin will try to kill Congressman DeVayne and that Cheryl and Johnny were murdered because they got in the way.
When the cops show up at the apartment building they talk to the doorman. He confirms that Congressman DeVayne is in his apartment and that a young woman is on her way up to see him. The woman is dressed exactly like Venus just as Cheryl was. The cops tell everyone to get down but she proceeds into the elevator. When they attempt to stop her the elevator doors close. The CSI team quickly runs up the stairs. Mac tries once more to get Congressman DeVayne on his mobile phone, but just as the congressman answers his phone the assassin aims her gun at his head. A silenced round is fired. By the time CSI gets up to the room the assassin is gone with the congressman murdered on the floor. Mac tells his team to start searching the other rooms and floors. Mac comes across a couple walking down the hall towards him. He stops them and tells them to go back to their apartment. Stella suddenly discovers the assassin's costume and radios everyone of her discovery. Mac yells out at the couple to stop, and the woman spins the man around pinning his arm behind his back. The assassin decides to shoot the man in the side so that she could get away. Mac momentarily stops to assist the fallen man and then takes off after the assassin. He follows her down the staircase to another floor of the building. He looks around for her and she is seen peaking out of a garbage chute. Mac hears the chute door close and throws it open expecting to find her hiding inside. But the assassin is nowhere to be found.